Addition of Rituximab to Chlorambucil Produces Superior Event-Free Survival in the Treatment of Patients With Extranodal Marginal-Zone B-Cell Lymphoma: 5-Year Analysis of the IELSG-19 Randomized Study

Zucca, Emanuele; Conconi, Annarita; Laszlò, Daniele; López‐Guillermo, Armando; Bouabdallah, Réda; Coiffier, Bertrand; Sebban, Catherine; Jardin, Fabrice; Vitolo, Umberto; Morschhauser, Franck; Pileri, Stefano; Copie‐Bergman, Christiane; Campo, Elı́as; Jack, Andrew; Floriani, Irene; Johnson, Peter; Martelli, Maurizio; Cavalli, Franco; Martinelli, Giovanni; Thiéblemont, Catherine

doi:10.1200/jco.2011.40.6272

Cited by 197 publications

(140 citation statements)

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“…6 Zucca et al have recently reported a randomised study comparing chlorambucil versus chlorambucil plus rituximab and concluded that although both treatments were active, a higher complete remission rate and 5-year event-free survival were achieved with combined therapy. 16 With regard to clinical and endoscopic presentation, in our series most patients presented with dyspeptic symptoms (only 11% showed B symptoms) and the more frequent endoscopic findings were erosions and ulcers most often localised in the antrum. This is in accordance with previous reports.…”

Section: Discussionmentioning

confidence: 99%

Gastric malt lymphoma: Analysis of a series of consecutive patients over 20 years

Moleiro

Ferreira

Lage

et al. 2015

United European Gastroenterology Journal

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Introduction and aims: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Helicobacter pylori (HP) infection. Our aim was to evaluate demographic, clinical and endoscopic characteristics of gastric MALT lymphoma patients, as well as to analyse response to treatment and factors that affect complete remission (CR) and relapse. We also assessed the long-term prognosis. Methods: The study involved a retrospective evaluation of consecutive patients admitted with gastric MALT lymphoma . Results: A total of 144 patients (76 men; mean age 56) were included. At stage EI, 94/103 patients (92%) received HP eradication and 78 (83%) achieved CR after a mean period of 7 months (2-63 months) and 67 (86%) remained in CR after a mean follow-up time of 105 months. HP infection status (p ¼ 0.004) and lymphoma localisation to the antrum plus body (p ¼ 0.016) were associated with higher and lower CR rates, respectively. Relapse occurred in 11/78 (14%) patients after a mean period of 21 months. The absence of HP re-infection (p ¼ 0.038), the need of only one eradication regimen (p ¼ 0.009) and antrum lymphomas (p ¼ 0.031) correlated with lower relapse rates. At stage EII, HP eradication was performed in 17/24 patients but only five experienced CR (30%). Among 16 patients diagnosed at stage EIV, nine achieved CR after chemotherapy AE surgery and 3/7 without remission died due to disease progression. The 5-and 10-year overall disease free survival rates were 90.5% and 79.1%, respectively. Conclusions: Most patients were diagnosed at an early stage. Eradication therapy was highly effective in inducing complete remission. Long-term evaluation showed that the long-term prognosis was very favourable.

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Section: Discussionmentioning

confidence: 99%

Gastric malt lymphoma: Analysis of a series of consecutive patients over 20 years

Moleiro

Ferreira

Lage

et al. 2015

United European Gastroenterology Journal

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“…Rituximab in combination with chemotherapy (alkylating agents or purine analogs) has shown ORRs of 85% to 93% (CR in 54% to 78%) in predominantly chemotherapynaive or treatment-naive patients. 4,5,9,12,26 In the relapsed setting, a retrospective analysis of 26 patients with extranodal MZL (no prior systemic antitumor therapy in 10 patients; 38%) treated with rituximab combined with cyclophosphamide, doxorubicin/mitoxantrone, vincristine, and prednisolone (R-CHOP or R-CNOP) showed an ORR of 77% (CR in 23%) with 85% of patients in continuous remission after a median follow-up of 19 months.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 Treatment of MZL ranges from localized to palliative approaches; however, for advanced disease, treatments range from single-agent chemotherapy or anti-CD20 monoclonal antibody to a more aggressive approach with chemoimmunotherapy. [4][5][6][7][8][9][10][11][12] Advanced disease is generally incurable, and the majority of patients will experience serial relapses. At the time of study initiation, no therapeutic agent was US Food and Drug Administration (FDA)-approved specifically for MZL, and no standard treatment existed.…”

Section: Introductionmentioning

confidence: 99%

Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma

Noy

Vos

Thiéblemont

et al. 2017

Blood

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251

198

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• Single-agent ibrutinib induced durable remissions (ORR 48%) with a favorable benefit-risk profile in patients with previously treated MZL.• Inhibition of BCR signaling with ibrutinib provides a treatment option without chemotherapy for an MZL population with high unmet need.Marginal zone lymphoma (MZL) is a heterogeneous B-cell malignancy for which no standard treatment exists. MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation. We conducted a multicenter, open-label, phase 2 study to evaluate the efficacy and safety of ibrutinib in previously treated MZL. Patients with histologically confirmed MZL of all subtypes who received ‡1 prior therapy with an anti-CD20 antibody-containing regimen were treated with 560 mg ibrutinib orally once daily until progression or unacceptable toxicity. The primary end point was independent review committee-assessed overall response rate (ORR) by 2007 International Working Group criteria. Among 63 enrolled patients, median age was 66 years (range, 30-92). Median number of prior systemic therapies was 2 (range, 1-9), and 63% received ‡1 prior chemoimmunotherapy. In 60 evaluable patients, ORR was 48% (95% confidence interval [CI], 35-62). With median follow-up of 19.4 months, median duration of response was not reached (95% CI, 16.7 to not estimable), and median progression-free survival was 14.2 months (95% CI, 8.3 to not estimable). Grade ‡3 adverse events (AEs; >5%) included anemia, pneumonia, and fatigue. Serious AEs of any grade occurred in 44%, with grade 3-4 pneumonia being the most common (8%). Rates of discontinuation and dose reductions due to AEs were 17% and 10%, respectively. Single-agent ibrutinib induced durable responses with a favorable benefit-risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy. As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL. This study is registered at www.clinicaltrials.gov as #NCT01980628. (Blood. 2017;129(16):2224-2232

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“…This trial compared chlorambucil alone to rituximab alone and to the combination of rituximab and chlorambucil (R-chlorambucil) as front-line therapy in MALT lymphoma patients, with event-free survival (EFS) as the primary endpoint. 23,24 Patients were stratified according to tumor site (gastric vs nongastric), nodal involvement, prior local therapy, and IPI risk group.…”

Section: Study Design and Data Collectionmentioning

confidence: 99%

“…We therefore sought to develop a MALT lymphoma IPI (MALT-IPI) for patients treated during the rituximab era by developing a model using the patient data set of the largest recent controlled clinical trial in MALT lymphoma, namely the International Extranodal Lymphoma Study Group 19 (IELSG-19) randomized study, conducted by the International Extranodal Lymphoma Study Group in 6 European countries, which showed the superiority of the combination of chlorambucil and rituximab in comparison with either rituximab or chlorambucil given as single agents. 23,24 Patients and methods…”

Section: Introductionmentioning

confidence: 99%

A MALT lymphoma prognostic index

Thiéblemont

Cascione

Conconi

et al. 2017

Blood

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163

124

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There are no widely accepted prognostic indices for extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). This study aimed to develop and validate a specific prognostic tool to personalize and optimize lymphoma treatment of patients with MALT lymphoma. A prognostic index was built by Cox regression (stepwise selection) using data from 401 patients enrolled in the international randomized IELSG-19 trial (NCT 00210353). A validation set, including 633 patients, was obtained by merging three independent cohorts of MALT lymphoma patients. The three individual features maintaining the greatest prognostic significance for event-free survival (EFS, the main endpoint of the IELSG-19 trial) were age ≥70 years (HR 1.72, 95% CI 1.26-2.33), Ann Arbor stage III or IV (HR 1.79, 95% CI 1.35-2.38), and elevated LDH level (HR 1.87, 95% CI 1.27-2.77). The prognostic index (MALT-IPI) constructed using these three parameters identified three groups: low, intermediate and high risk (corresponding to the presence of 0, 1 or ≥2 of these factors, respectively). The 5-year EFS rates in the low, intermediate and high risk groups were 70%, 56% and 29%, respectively. The MALT-IPI also significantly discriminated between patients with different progression-free, overall and cause-specific survival. The prognostic utility was retained in gastric and non-gastric lymphomas, in each treatment arm (chlorambucil, rituximab, rituximab plus chlorambucil), and was confirmed in the validation set. The new index, MALT-IPI, is a simple, accessible and effective tool to identify MALT lymphoma patients at risk of poor outcomes. It may help define appropriate treatment approaches for individual patients

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Addition of Rituximab to Chlorambucil Produces Superior Event-Free Survival in the Treatment of Patients With Extranodal Marginal-Zone B-Cell Lymphoma: 5-Year Analysis of the IELSG-19 Randomized Study

Abstract: Both treatments were active; the better response rate and EFS obtained with the addition of rituximab did not translate into improved OS.

Cited by 197 publications

References 25 publications

Gastric malt lymphoma: Analysis of a series of consecutive patients over 20 years

Gastric malt lymphoma: Analysis of a series of consecutive patients over 20 years

Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma

A MALT lymphoma prognostic index

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